Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk

A. M. Harriott, M. G. Heckman, S. Rayaprolu, A. I. Soto-Ortolaza, N. N. Diehl, Takahisa Kanekiyo, Chia-Chen Liu, Guojun D Bu, R. Malik, J. W. Cole, James F Meschia, Owen A Ross, the METASTROKE Consortium for the METASTROKE Consortium

Research output: Contribution to journalArticle

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Abstract

Background and purpose: Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). Methods: A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. Results: In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). Conclusions: The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.

Original languageEnglish (US)
Pages (from-to)1235-1241
Number of pages7
JournalEuropean Journal of Neurology
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2015

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Low Density Lipoprotein Receptor-Related Protein-6
Low Density Lipoprotein Receptor-Related Protein-1
Stroke
Genes
Odds Ratio
African Americans

Keywords

  • Genetics
  • Ischaemic stroke
  • Low density lipoprotein receptor related protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Harriott, A. M., Heckman, M. G., Rayaprolu, S., Soto-Ortolaza, A. I., Diehl, N. N., Kanekiyo, T., ... for the METASTROKE Consortium, T. METASTROKE. C. (2015). Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk. European Journal of Neurology, 22(8), 1235-1241. https://doi.org/10.1111/ene.12735

Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk. / Harriott, A. M.; Heckman, M. G.; Rayaprolu, S.; Soto-Ortolaza, A. I.; Diehl, N. N.; Kanekiyo, Takahisa; Liu, Chia-Chen; Bu, Guojun D; Malik, R.; Cole, J. W.; Meschia, James F; Ross, Owen A; for the METASTROKE Consortium, the METASTROKE Consortium.

In: European Journal of Neurology, Vol. 22, No. 8, 01.08.2015, p. 1235-1241.

Research output: Contribution to journalArticle

Harriott, AM, Heckman, MG, Rayaprolu, S, Soto-Ortolaza, AI, Diehl, NN, Kanekiyo, T, Liu, C-C, Bu, GD, Malik, R, Cole, JW, Meschia, JF, Ross, OA & for the METASTROKE Consortium, TMETASTROKEC 2015, 'Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk', European Journal of Neurology, vol. 22, no. 8, pp. 1235-1241. https://doi.org/10.1111/ene.12735
Harriott, A. M. ; Heckman, M. G. ; Rayaprolu, S. ; Soto-Ortolaza, A. I. ; Diehl, N. N. ; Kanekiyo, Takahisa ; Liu, Chia-Chen ; Bu, Guojun D ; Malik, R. ; Cole, J. W. ; Meschia, James F ; Ross, Owen A ; for the METASTROKE Consortium, the METASTROKE Consortium. / Low density lipoprotein receptor related protein 1 and 6 gene variants and ischaemic stroke risk. In: European Journal of Neurology. 2015 ; Vol. 22, No. 8. pp. 1235-1241.
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abstract = "Background and purpose: Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). Methods: A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. Results: In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0{\%} of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). Conclusions: The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.",
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AU - Heckman, M. G.

AU - Rayaprolu, S.

AU - Soto-Ortolaza, A. I.

AU - Diehl, N. N.

AU - Kanekiyo, Takahisa

AU - Liu, Chia-Chen

AU - Bu, Guojun D

AU - Malik, R.

AU - Cole, J. W.

AU - Meschia, James F

AU - Ross, Owen A

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N2 - Background and purpose: Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). Methods: A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. Results: In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). Conclusions: The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.

AB - Background and purpose: Low density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS). Methods: A Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke. Results: In the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non-carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006). Conclusions: The results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.

KW - Genetics

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KW - Low density lipoprotein receptor related protein

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